What’s happening inside the brain on LSD? Colorado psychedelics legislation flies through state Senate, and Oregon gets its first licensed testing lab

Plus: An active placebo, and highlights and challenges in psychedelic business

Happy Friday, and welcome back to The Microdose, an independent journalism newsletter brought to you by the U.C. Berkeley Center for the Science of Psychedelics. 

What’s happening inside the brain on LSD?

It’s well known that psychedelics often cause hallucinogenic effects, but scientists are still figuring out why that is. In a study published this week in the journal Neuropsychopharmcology, researchers probe what happens in the brain as people trip on LSD. Researchers analyzed data from 45 participants who took part in two experimental sessions. In each session, researchers recorded the participants’ baseline brain activity using functional magnetic resonance imaging, or fMRI. Next, they were given a capsule, which contained either a placebo or 100 micrograms of LSD, and their brains were scanned again around two hours after they ingested the pill. 

When participants were given LSD, they showed stronger connections between brain regions and reduced self-inhibition compared to those who received the placebo. (Other studies have suggested that psilocybin also increases brain connectivity.) The researchers say that LSD appears to alter the brain’s balance of excitatory and inhibitory activity, or E/I. “This is especially relevant because disturbances in the E/I balance have been discussed in the context of psychosis and more recently in the context of psychedelic-induced hallucinations and synaesthesia,” they write. 

Moreover, they found that using their brain connectivity data, a machine-learning model was 91% accurate in predicting which participants experienced subjective effects during LSD sessions.

The Latest in Colorado: SB 290 flies through state Senate

This week the Colorado senate voted to pass Senate Bill 290, which adopts policies to implement Proposition 122, or the Natural Medicine Health Act (NMHA). Colorado voters passed the NMHA in November 2022, establishing psilocybin services in the state and making the use of natural medicines state-legal. Colorado Senator Steve Fenberg (D) introduced SB 290 just last Tuesday. The Senate Finance Committee held a public hearing on Friday, in which dozens of speakers voiced their concerns about SB 290 and their support for the use of psychedelic medicines. Attorney Mason Marks detailed the meeting in a recent issue of his newsletter. He reports that some speakers raised concerns about the lack of inclusion and exploitation of Indigenous communities, as well as about harm reduction and safety.

After the hearing, the senate amended the bill to specifically mention and allow for traditional tribal or Indigenous use of natural medicines, and to allow individuals to obtain lab testing results for psychedelics for personal use. It also specifies a budget of over $733,000 to implement SB 290. The bill now moves to the House.

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The Latest in Oregon: The first licensed testing lab 

Oregon Psilocybin Services (OPS) has officially licensed its first psilocybin testing lab: Rose City Laboratories. (For more on lab testing, read our interview with Rose City’s senior chemist Bjorn Fritzsche.) For psilocybin services to begin in the state, OPS still needs to license service centers. According to OPS records, the agency has received 17 service center applications but none have been approved yet. 

The cost of obtaining those licenses — more than $10,000 — and the potentially high costs of state-legal psilocybin are driving some practitioners underground, according to a new piece in Willamette Week. “Facilitators, some of them newly graduated from trip training programs, are leading sessions in their homes, in Airbnbs, and on psychedelic retreats abroad. Amateur mycologists are growing hundreds of grams of Psilocybe cubensis in plastic tubs in basements around town,” writes Anthony Effinger, who spoke with facilitators and growers who have been operating outside Oregon’s burgeoning licensing system for years. Many expressed concerns that the high costs of operating an official, licensed business would prevent people from accessing services. “Many graduates of Oregon’s training programs are getting dunked right now,” Effinger writes. “They stumped up thousands for training and having no place to practice.”

An active placebo

This week, Frontiers in Psychiatry published Yale researchers’ study protocol for a randomized, controlled clinical trial studying the efficacy of psilocybin in treating obsessive compulsive disorder. In the study, which began in 2018 and continues through October 2023, 36 participants are receiving either a moderate dose of psilocybin or a placebo. Because the study is ongoing, the results are not yet available, but the protocol included an interesting note about the trial’s use of placebo: they’re using 250 milligrams of niacin, or vitamin B3, which is known to induce side effects at that dosage. The psilocybin and niacin capsules look, taste, and smell the same, the authors write, and niacin “may also induce mild psychological (e.g., anxiety) and physiological effects (e.g., hot flushes, tingling sensations, increased heart rate) similar to low to moderate doses of psilocybin.” Many psychedelic trials have no active placebo, a fact that concerns many researchers; if participants can accurately guess whether they’ve received a psychedelic or a placebo, their expectations may bias study outcomes. The studies that do use placebos often use a very low dose of the psychedelic under study or an inactive placebo such as lactose pills. The Yale researchers’ study is not the first to use niacin as an active placebo, but the study protocol suggests one potential way forward for blinding issues in psilocybin studies.

Highlights and challenges in psychedelic business

Psychedelics business insights company reMind released its first annual report, produced by Psychedelic Alpha’s Josh Hardman. The report provides an overview of the psychedelic industry and major milestones in research and legislation. Hardman describes various “trends” and “tensions” in the field, including psychedelic companies’ patent wars, the cost and accessibility of psychedelic-assisted therapy, hoped-for “next-gen” psychedelic molecules modified to remove hallucinogenic effects, and the lack of insurance coverage of psychedelic treatments. Hardman writes that insurance companies might be more inclined to provide coverage of psychedelics if there were stronger real-world evidence to support their efficacy. He predicts we’ll see more such data collection in the next few years, perhaps through “electronic health records, consumer wearable devices, [and] data relating to insurance claims,” he writes.

• Bend Bulletin interviews Oregon’s first three licensed psilocybin facilitators, who include an artist, a former alpaca and hemp farmer, and a flight instructor. 

• Sam Altman, chief executive of the lab that created ChatGPT, is also chairman of psychedelics start-up Journey Colab. “Altman’s foray into psychedelics showcases the buzz that the drugs have kindled in Silicon Valley, with venture capitalists betting millions of dollars that such therapies will transform treatment for mental health disorders and drug addiction,” writes The Washington Post. 

• Spectrum reports on Nova Mentis Life Science’s clinical trial on the efficacy of psilocybin in treating fragile X syndrome, a genetic condition that affects early development. The trial began recruiting participants last week.

• Former pro athletes are turning to psilocybin to treat their anxiety, depression, and chronic pain. In a feature collaboration, ESPN and KFF Health News reporters profile athletes including boxer Mike Lee and former pro-hockey player Riley Cote as they seek healing through a psychedelic retreat.

You’re all caught up! Have a great weekend. We’ll be back in your inbox on Monday with a new issue of 5 Questions.

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